5-94775610-T-G

Variant names:

• chr5-94775610-T-G
• rs255375
• NM_024717.7:c.2610+3500A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024717.7(MCTP1):​c.2610+3500A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,950 control chromosomes in the GnomAD database, including 19,059 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (19059 hom., cov: 32)
• Consequence: MCTP1 NM_024717.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

Genes affected

MCTP1 (HGNC:26183): (multiple C2 and transmembrane domain containing 1) Enables calcium ion binding activity. Predicted to be involved in several processes, including modulation of chemical synaptic transmission; negative regulation of endocytosis; and negative regulation of response to oxidative stress. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCTP1	NM_024717.7	c.2610+3500A>C		intron_variant	Intron 19 of 22	ENST00000515393.6	NP_078993.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCTP1	ENST00000515393.6	c.2610+3500A>C		intron_variant	Intron 19 of 22	1	NM_024717.7	ENSP00000424126.1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75236 AN: 151832 Hom.: 19033 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.500

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.496 AC: 75320 AN: 151950 Hom.: 19059 Cov.: 32 AF XY: 0.497 AC XY: 36908 AN XY: 74270

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.645

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.502

Alfa AF: 0.422 Hom.: 2919

Bravo AF: 0.502

Asia WGS AF: 0.615 AC: 2139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0060
DANN	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs255375; hg19: chr5-94111315; COSMIC: COSV56502823;